Pharmacology Exam 4

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Two types of PD
- idiopathic
- drug induced
Idiopathic PD
- progressive neurodegenerative disorder
- loss of dopaminergic neurons in the substantia nigra
- lewy bodies
Drug-induced PD
- DA receptor antagonists
- haloperidol
- thorazine
- prochlorperazine
- metoclopramide
- MPTP
3 symptoms of PD
- bradykinesia or akinesia
- resting tremor
- muscular rigidity or hypertonicity
Mechanisms to treat PD
- replacement therapy with dopamine
- decrease cholinergic neurotransmissions
Anticholinergic anti PD drugs
- muscarinic acetylcholine receptor antagonsits
- Trihexyphenidyl
- Benztropine
Therapeutic application of muscarinic acetylcholine receptor antagonists
- mild idiopathic PD
- use with L-dopa for severe idiopathic PD
- use for drug induced PD
Side effects of Anticholinergic anti PD drugs
- drowsiness
- mental slowness
- tachycardia
- dry mouth
- constipation
Contraindications to anticholinergic anti PD drugs
- prostatic hyperplasia
- obstructive GI disease
- angle closure glaucoma
Biosynthesis pathway for DA

tyrosine =(tyrosine hydroxylase)=> DOPA =(decarboxylase)=> dopamine
Mechanism of action of L-Dopa

L-DOPA is converted to DA in the basal ganglia
4 issues after long treatment with L-DOPA
- diminished effectiveness (3-4 years)
- levodopa dose not stop the progression of PD
- Wearing off and end of dose akinesia
- on/off phenomenon
Side effects of anti PD drugs
- stimulation of emetic center
- tachycardia and orthostatic hypotension
- dyskinesia 80% of pt
- behavioral agitation or delirium
- hormonal problems (DA stops prolactin)
Interaction of anti PD drugs with pyridoxine

amino acid decarboxylase cofactor
Interaction of anti PD drugs with MAOIs

hypertensive crisis
Interactions of anti-PD drugs with antipsychotics

Levodopa prohibited in psychotic patients
Drug interactions of anti-PD agents with physostigmine

cholinesterase inhibitor used for glaucoma
Carbidopa
- peripheral decarboxylase inhibitor
- decreases DA in peripheral circulation by conversion of levodopa
- reduces requirement of levodopa by 75%
- do not use in antipsychotic induced PD
DA receptor agonists
- Bromocriptine D2
- Perglide D1 and D2
- Ropinirole D2
- Pramipexole D3
- Rotigotine (patch)
Levodopa bioavailability

1-3% passes through BBB
Bioavailability of Levodopa with Carbidopa
- carbidopa inhibits degredation in the periphery
- 10% available to cross BBB
Applications for other DA receptor agonists
- better for on/off phenomenon
- useful for those who cannot tolerate side effects
- similar GI and cardiovascular toxicities as L-DOPA
- contraindicated in psychotic illness or recent MI ro GI ulcer
Amantadine
- decreases DA reuptake, increases DA release
- anticholinergic effects
- antiviral compound
- use with caution in pt with renal failure, CHF and seizures
Selegiline
- MAOI
- irreversible
- decreases "wearing off" of L-DOPA
- delays initiation of L-DOPA therapy for PD treatment
Entacapone
- short duration
- peripheral COMT inhibitor
Tolcapone
- long duration
- actis in CNS and periphery
- COMT inhibitor
- 2% hepatotoxicity
Stalevo
- carbidopa
- levodopa
- entacapone
Surgical procedures for anti PD
- deep brainstem stimulator
- tissue transplant
Block mACH receptor
- trihexyphenidyl
- benztropine
- amantadine
stimulate D2 receptors on the post synaptic neuron
- ropinirole
- bromocriptine
- pergolide
Neurodegenerative diseases
- PD
- Huntingtons Disease
- alzheimer's disease
- ALS (amyotrophic lateral sclerosis) (lou gherig's)
PD and Huntington's disease

loss of neurons in the basal ganglia and abnormalities in control of movement
Alzheimer's disease
- loss of hippocampal and cortical neurons
- imparement of memory and cognitive ability
ALS
- degeneration of spinal, bulbar and cortical motor neurons
- muscular weakness
- speak, swallow and facial expression
Factors for Neurodegenterative disorders
- genetic
- environmental
- excitotoxicity
- oxidative stress
Function of Drugs for AD

augment cholinergic function in the brain
Cholinesterase inhibitors used for AD
- tacrine
- donepezil
- rivastigmine
- galantamine
NMDA antagonist used to treat AD

memantine
Mechanism of drugs for ALS
- inhibit glutamate release
- block glutamate receptors
- relieves spasticity
Drugs for ALS
- GABAb agonists : Baclofen
- A2 adrenergic agonists: tizanidine
Tardive dyskinesia

caused by DA receptor blocker
Tardive dystonia

da receptor blocker or anticholinergic drugs
tardive akathisia

anticholinergic anti PD
restless leg syndrome
- pramipexole
- ropinirole

Author

Rx2013

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Card Set

Pharmacology Exam 4

Description

Treatment for PD and other neurodegenerative diseases

Updated

2010-11-13T20:12:26Z

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